Histone lysine demethylase 4B regulates general and unique gene expression signatures in hypoxic cancer cells

Lei Qiu, Yang Meng, Lingli Wang, Sumedha Gunewardena, Sicheng Liu, Junhong Han, Adam J. Krieg

Research output: Contribution to journalArticlepeer-review

Abstract

The hypoxic tumor microenvironment promotes tumor survival by inducing the expression of genes involved in angiogenesis and metastasis. As a direct target of hypoxia-inducible factor, lysine demethylase 4B (KDM4B) is overexpressed in multiple cancers, suggesting that a general KDM4B regulatory mechanism may exist in these cancer types. In this study, we sought to further investigate the general and unique roles of KDM4B in ovarian, colon, and renal cancer cells. We first identified a set of potential KDM4B targets shared by SKOV3ip.1, HCT116, and RCC4 cell lines, as well as numerous genes specifically regulated in each cell line. Through Gene Ontology, KEGG, and Oncobox pathway analyses, we found that KDM4B primarily regulated biosynthetic and cell cycle pathways in normoxia, whereas in hypoxia, it regulated pathways associated with inflammatory response and migration. TCGA data analyses reveal high expression of KDM4B in multiple cancer types and differential expression across cancer stages. Kaplan–Meier plots suggest that elevated KDM4B expression may contribute to a better or worse prognosis in a manner specific to each cancer type. Overall, our findings suggest that KDM4B plays complex roles in regulating multiple cancer processes, providing a useful resource for the future development of cancer therapies that target KDM4B expression.

Original languageEnglish (US)
Pages (from-to)414-429
Number of pages16
JournalMedComm
Volume2
Issue number3
DOIs
StatePublished - Sep 2021

Keywords

  • colorectal cancer
  • histone lysine demethylase 4B
  • ovarian cancer
  • renal cell carcinoma
  • tumor hypoxia

ASJC Scopus subject areas

  • Biochemistry, medical
  • Genetics(clinical)
  • Immunology and Allergy
  • Oncology
  • Cell Biology
  • Genetics
  • Drug Discovery
  • Computer Science Applications

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